Study on the pathogenic mechanisms and clinical treatment of advanced glycation end products (AGEs) in diabetic complications

Abstract

The accumulation of Advanced Glycation End Products (AGEs), resulting from the Maillard Reaction formed via exogenous intake from food and a hyperglycemic internal environment in the body, can cause or exacerbate various complications of Diabetes Mellitus. This article discusses the chemistry of AGEs formation and their pathobiochemistry, with a particular focus on the cardiovascular system, musculoskeletal system, and peripheral nervous system, which significantly affect population health. AGEs not only alter the normal physiological state of the system in a high-glucose environment through cross-linking with tissues and cells and related metabolites, but also induce the release of inflammatory factors and reactive oxygen species through multiple pathways, including NF-κB and NADPH pathways, by binding to receptors, and regulate the p38 and JNK pathways, affecting the imbalance of osteoclasts and osteoblasts. This review, drawing upon clinical studies, explores both conventional and novel detection methods for AGEs, along with their associated limitations, and suggests their potential as biomarkers and therapeutic targets for associated diseases. The review also discusses emerging therapeutic strategies aimed at reducing AGE accumulation and inhibiting AGE–RAGE interactions. These methods include natural products such as resveratrol and chrysin, as well as related inhibitors that exert their effects through competitive inhibition and by altering their active states. Unlike previous studies that primarily focus on a single system, diabetes typically causes complications in multiple organ systems. By elucidating both the shared and system-specific mechanisms of AGE action, and summarizing intervention strategies and the application of novel inhibitors, this review aims to provide new insights into the clinical treatment and prevention of diabetic complications.